IL-17A/p38 Signaling Pathway Induces Alveolar Epithelial Cell Pyroptosis and Hyperpermeability in Sepsis-Induced Acute Lung Injury by Activating NLRP3 Inflammasome.

Sepsis is a syndrome with poor prognosis. Nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and T helper 17 (Th17) cells are involved in the pathogenesis of inflammatory diseases. This study aims to explore their roles and underlying mechanisms in sepsis. The blood and bronchoalveolar lavage fluid are collected from sepsis patients and healthy donors. A sepsis mice model is established by cecal ligation puncture (CLP). The contents of cytokines are detected by ELISA. The amounts of Th17 cells, IL-17A, IL-1ß, IL-18, and lipopolysaccharide is significantly elevated in sepsis patients. The increased differentiation of Th17 cells can promote lung cell pyroptosis and induce hyperpermeability via activating NLRP3 inflammasome and p38 pathway. The inhibitors targeting Th17 cells, NLRP3 inflammasome, and p38 pathway can significantly alleviate lung injury in sepsis mice. Th17 cells can secrete IL-17A to activate NLRP3 inflammasome via p38 signaling pathway, which contributes to the development of sepsis-induced acute lung injury.

The immunomodulation role of Th17 and Treg in renal transplantation.

Kidney transplantation (KT) is an ultimate treatment of end-stage chronic kidney disease, which can meet a lot of complications induced by immune system. With under-controlled immunosuppression, the patient will obtain a good prognosis. Otherwise, allograft disfunction will cause severe organ failure and even immune collapse. Acute or chronic allograft dysfunction after KT is related to Th17, Treg, and Th17/Treg to a certain extent. Elevated Th17 levels may lead to acute rejection or chronic allograft dysfunction. Treg mainly plays a protective role on allografts by regulating immune response. The imbalance of the two may further aggravate the balance of immune response and damage the allograft. Controlling Th17 level, improving Treg function and level, and adjusting Th17/Treg ratio may have positive effects on longer allograft survival and better prognosis of receptors.

Preliminary Study on the Combination Effect of Clindamycin and Low Dose Trimethoprim-Sulfamethoxazole on Severe Pneumocystis Pneumonia After Renal Transplantation.

Objective: Evaluate the effect of the combination of clindamycin with low-dose trimethoprim-sulfamethoxazole (TMP/SMX) regimen on sever Pneumocystis pneumonia (PCP) after renal transplantation. Method: 20 severe PCP patients after renal transplantation were included in this historical-control, retrospective study. A 10 patients were treated with the standard dose of TMP/SMX (T group), the other 10 patients were treated with the combination of clindamycin and low dose TMP/SMX (CT group). Results: Although there was no significant difference in the hospital survival between the two groups, the CT protocol improved the PaO2/FiO2 ratio more significantly and rapidly after the 6th ICU day (1.51 vs. 0.38, P = 0.014). CT protocol also ameliorated the pulmonary infiltration and the lactate dehydrogenase level more effectively. Moreover, the CT protocol reduced the incidence of pneumomediastinum (0 vs. 50%, P = 0.008), the length of hospital staying (26.5 vs. 39.0 days, P = 0.011) and ICU staying (12.5 vs. 22.5 days, P = 0.008). Furthermore, more thrombocytopenia (9/10 vs. 3/10, P = 0.020) was emerged in the T group than in the CT group. The total adverse reaction rate was much lower in the CT group than in the T group (8/80 vs. 27/80, P < 0.001). Consequently, the dosage of TMP/SMX was reduced in 8 patients, while only 2 patients in the CT group received TMP/SMX decrement (P = 0.023). Conclusion: The current study proposed that clindamycin combined with low-dose TMP/SMX was more effective and safer the than single use of TMP/SMX for severe PCP patients after renal transplantation (NCT04328688).

Neutrophil-to-Lymphocyte Ratio Predicts Mortality in Adult Renal Transplant Recipients with Severe Community-Acquired Pneumonia.

Mortality of renal transplant recipients with severe community-acquired pneumonia (CAP) remains high, despite advances in critical care management. There is still a lack of biomarkers for predicting prognosis of these patients. The present study aimed to investigate the association between neutrophil-to-lymphocyte ratio (NLR) and mortality in renal transplant recipients with severe CAP. A total of 111 renal transplant recipients with severe CAP admitted to the intensive care unit (ICU) were screened for eligibility between 1 January 2009 and 30 November 2018. Patient characteristics and laboratory test results at ICU admission were retrospectively collected. There were 18 non-survivors (22.2%) among 81 patients with severe CAP who were finally included. Non-survivors had a higher NLR level than survivors (26.8 vs. 12.3, p < 0.001). NLR had the greatest power to predict mortality as suggested by area under the curve (0.88 ± 0.04; p < 0.0001) compared to platelet-to-lymphocyte ratio (0.75 ± 0.06; p < 0.01), pneumonia severity index (0.65 ± 0.08; p = 0.05), CURB-65 (0.65 ± 0.08; p = 0.05), and neutrophil count (0.68 ± 0.07; p < 0.01). Multivariate logistic regression models revealed that NLR was associated with hospital and ICU mortality in renal transplant recipients with severe CAP. NLR levels were independently associated with mortality and may be a useful biomarker for predicting poor outcome in renal transplant recipients with severe CAP.

Lactate dehydrogenase as a prognostic marker of renal transplant recipients with severe community-acquired pneumonia: a 10-year retrospective study.

BACKGROUND: Lactate dehydrogenase (LDH) is an easily accessible biological marker that has been associated with several pulmonary disorders. The aim of this study was to investigate the prognostic value of serum LDH in renal transplant recipients with severe community-acquired pneumonia (CAP). METHODS: A total of 77 renal transplant recipients with severe CAP admitted to the intensive care unit (ICU) were screened for eligibility in this retrospective study. Patient characteristics and laboratory tests, such as LDH on day 1 (LDHday 1) and day 3 (LDHday 3) were recorded. Cox regression models were used to assess the performance of LDH to predict 90-day mortality. RESULTS: Median LDH level was higher on day 1 in 90-day nonsurvivors (440 U/L, IQR, 362-1,055 U/L) than in survivors (334 U/L, IQR, 265-432 U/L; P<0.001); median LDH level on day 3 in nonsurvivors was 522.5 U/L (IQR, 457.5-1,058.5 U/L) and in survivors 290 U/L (IQR, 223-387.5 U/L; P<0.001). Analysis of LDH kinetics from day 1 to day 3 showed an increase in nonsurvivors and a decrease in survivors. Moreover, Multivariate Cox analysis showed that LDHday 1 (increase per 100 U/L), LDHday 3 (increase per 100 U/L) and LDH kinetics (increase per 10%) were independently associated with 90-day mortality. CONCLUSIONS: Serum LDH levels and LDH kinetics early were independently associated with 90-day mortality in renal transplant recipients with severe CAP. In future, the prognostic role of LDH needs to be warranted.